P480: NKG2D-MEDIATED ANTI-TUMOR IMMUNITY CONTRIBUTES TO THE FAVORABLE PROGNOSIS IN APL
Authors: H. Wang, X. Zhang, S. Gong, H. Du, N. Mei
Journal: HemaSphere (2022)

Background: Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor prognosis. Acute promyelocytic leukemia (APL) is a unique subtype of AML, with PML-RARA fusion caused by t(15;17)(q22;q12) translocation, and is now considered a highly curable disease. Exploring the difference between APL and non-APL AML, may shed new insight on the treatment of AML. NKG2D is an activating receptor on NK cells that recognizes ligands on the surface of tumor cells and plays a crucial role in tumor cell killing. Prior studies have demonstrated that one mechanism of AML immune evasion is downregulation of NKG2D ligands (NKG2DL) or secretion of receptor-blocking soluble ligands. Whereas, reports on NKG2DL expression in APL are still lacking. In this study, we investigate the differences of NKG2DL expression on APL and non-APL cells. Aims: Exploring the difference between APL and non-APL AML, may shed new insight on the treatment of AML. Methods: Bone marrow samples were derived from de novo APL and non-APL AML patients, diagnosed according to French-American-British (FAB) criteria in The First Affiliated Hospital of Xi’an Jiao Tong University. Flow cytometry was performed with the anti-NKG2DL mAbs (MIC-A/B-PE, ULBP-1-APC, ULBP-2/5/6-PerCP). Leukemic blasts were identified using the CD45/SSC gating procedure. Non-APL AML patients were divided into high or low group based on the median expression levels of NKG2DL for survival analysis. Results: Totally 46 patients comprising of 23 APL and 23 non-APL AML were enrolled in this study. There was no significant difference in the baseline characteristics between the two groups. All non‐APL AML cells had low or no NKG2DL surface expression, while most APL cells expressed high NKG2DL levels. In particular, just two APL patients was negative for the NKG2DL but positive for CD34. The median percentage of NKG2DL among non-APL AML cells and APL cells were 1.2% vs 20.3% in MIC-A/B (P<0.01), 1.1% vs 54.8% in ULBP-1 (P=0.017), and 3.8% vs 36.35% in ULBP-2/5/6 (P<0.01). (Fig.1) 23 non-APL AML patients were enrolled for study inclusion; one patient dropped out due to cerebral infarction. The median follow-up time was 17.2 weeks. The high ULBP-2/5/6 group showed a superior overall survival rate compared to the low ULBP-2/5/6 group (P < 0.01), but there was no significant difference between high and low MIC-A/B groups (P = 0.31) or between the high and low ULBP-1 groups (P = 0.52). Image:Summary/Conclusion: NKG2DL was decreased significantly on the surface of non-APL AML cells compared with APL cells. These results may indicate that NKG2D-mediated anti-tumor immunity contributes to the favorable prognosis in APL, while immune escape is an underlying mechanism for unfavorable prognosis in non-APL AML. NKG2DL may be used as a potential biomarker to predict prognosis of patients with non-APL AML, and upregulation of its expression could improve the clinical efficacy. Further studies with larger sample size and longer follow-up are required to confirm our conclusion.